Abstract A004: Developing ovarian cancer xenograft in mouse model to see FSHR-mediated anticancer effect of Moringa oleifera root extract

Abstract

Abstract Introduction: Sex hormones play an important role in ovarian cancer as novel redirected T-cell-based immunotherapy targeting human follicle-stimulating hormone receptor (FSHR)is tried. Moringa olifera root extract has shown efficacy in cancer cell as well as in hormonal milieu of ovary and reproductive organ. Hence, the aim of the present study was to study the anticancer effect of Moringa oleifera on human OAW 42 & MCF-7 cell line through its putative FSHR antagonistic role. Methods: The colorimetric MTT metabolic activity assay was used to see cell viability. Western blot analysis was performed to check its effect in apoptosis. Clonogenic assay was carried out to see the effect of Moringa root extract on cancer cell proliferation. Cell cycle analysis was done based on incorporation of Propidium Iodide into DNA (BD Cycletest™ Plus DNA Kit). Analyses of the samples were carried out flow cytometrically using BD LSRFortessaTM SORP (San Jose, CA) cell analyzer and BD FACSDiva v8.0.1 software.On day 35, mice were sacrificed and histopathologic analysis of the ovaries was carried out following standard protocol followed by IHC for detection of FSHR. Result: The dose-dependent analysis on viability of OAW-42 and MCF-7 cells by MTT assay showed 50% lethal toxicity (IC-50) of MRE (Moringa root extract) to be 250µg/ml and 200µg/ml, respectively, with synergestic effect of Moringa extract with both cisplatin and paclitaxol in OAW-42 cell line. Moringa extract at its IC-50 value showed visible effect in case of cleaved caspase-9. In clonogenic assay approximately 40% reduction of colony formation was observed. Flow cytometric data showed that after 24 hours and 48 hours of treatment with MOL root extract at its IC-50 dose, DNA content progressively increased in the sub G0 phase. However, approximately 3% upregulation and 11.4% downgulation of PI intensity at G0/G1 phase was also observed. Profuse expression of FSHR and its downstream target cMyc in the stroma of carcinoma control mice compared to control or Moringa-treated mice. Conclusion: We can conclude that MRE is a promising candidate for treatment of ovarian cancer by an FSHR-mediated pathway either alone or in combination with traditional chemotherapeutic drugs like cisplatin and paclitaxol at a sublethal dose of their toxicity. Citation Format: Chinmay Kumar Basu. Developing ovarian cancer xenograft in mouse model to see FSHR-mediated anticancer effect of Moringa oleifera root extract [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A004.